A Comparative study between the effect of oxytocin and human chorionic gonadotropin on induction of ovulation

INTRODUCTION

Oxytocin (OT) can be regarded as a good choice for inducing ovulation in anovulatory women. Oxytocin, a natural hormone, has some receptors and is generated by some reproductive organs. The pre-ovulatory existence of mRNAs, the oxytocin receptor, in granulosa cells indicates the role played by oxytocin in the follicular development. Being a neuropeptide, OT has been demonstrated to have a probable role in the ovulation process. Oxytocin is primarily generated in two hypothalamus nuclei, from which it is discharged into CSF, directly into the circulation, anterior pituitary, and portal system, and it affects gonadotropin secretion. A lot of novel treatment modalities have been presented in recent years with no suitable assessment of their efficacy and safety.¹

Laboratory evidences focus on the role of oxytocin in influencing the anterior pituitary hormones as a hypothalamus regulatory factor. Since gonadotropin and oxytocin releasing hormone functions as competing substrates for hypothalamus-degrading enzymes, the

assumption is that OT secretion in the middle of monthly period in portal blood can inhibit GnRH metabolism and increase the amount of GnRH available.²

Human chorionic gonadotropin (HCG) is a hormone produced by the placenta that is first produced by cells (syncitiotrophoblasts) from the implanting conceptus in week 2 to support the ovarian corpus luteum, which in turn maintains the lining of the endometrium and thus keeps the pregnancy.³

The majority of pregnancy tests are based on the hormone found in maternal blood and urine.The protein performs a variety of different functions; include promoting the initiation of embryonic gonadal steroidogenesis, and high concentrations were discovered to be a teratogen to embryonic gonadal tissues. Other probable cellular origins include cytotrophoblast cells producing hyper-glycosylated HCG, several main non-trophoblastic cancers producing free beta-subunit, and pituitary HCG generated via anterior pituitary gonadotrope cells. The glycoprotein hormone family includes the pituitary hormones thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH).⁴

It is believed that HCG may be mediating relevant reproductive processes. Low-dose HCG could also be utilized to imitate LH activities on growing follicles in a more steady and sustained way, allowing folliculogenesis to progress once LH/HCG receptors are expressed in the GC of bigger follicles of the ovary. This method has the ability to mimic hormone dynamics during the normal follicular stage, potentially lowering the likelihood of issues like the ovarian hyper stimulation syndrome.⁵

Low-dose HCG can be administered to patients being stimulated for assisted reproduction to complete folliculogenesis. A previous study found that low-dose HCG was much more effective than a conventional regimen at achieving pregnancies. This approach to ovarian stimulation represents an effective and economic alternative.⁶

The goal of the research was to compare the effects of oxytocin and human chorionic gonadotrophin.

PATIENTS AND METHODS

A randomised prospective interventional trial was conducted in this study. The data was collected from the patients assigned according to exclusion and inclusion criteria at Al-Hussein Al-Azhar University Hospital and Dar Ismael Hospital from May 2019 to May 2020.

Our target population was 100 participants suffering from anovulation, who were randomly assigned to one of two equal groups to undergo either: Group A: 50 patients (10.000 IU) Human Chorionic Gonadotrophins (Choriomon) made by IBSA Institute Biochimique SA, CH-6903 Lugano. Group B: 50 patients (5 IU) Oxytocin (Syntocinon) manufactured by (Sandoz, New jersey, USA) intramuscularly. From day 2 to day 6, clomiphene citrate stimulation (100 mg/day) resulted in enlarged ovarian follicles (diameter > 18 mm).

Inclusion criteria: Chronic anovulation, primary or secondary infertility, patients between the ages of 21 and 39, patent tubes on hysterosalpingography, without pelvic disease, and normal semen analysis

Exclusion criteria: Had a history of cardiovascular disease and hypersensitivity to any drugs, uterine abnormalities: septum, polyp, myoma, patients with abnormal thyroid function, patients with hyperprolactimemia, patients with primary anovulation (FSH ≤10), patients not responding to induction, uncontrolled diabetes, obesity and under weight, and patients with excessive response (Over stimulation).

All Patients subjected to:

History:

A thorough workup ought to be undertaken before beginning any infertility therapy to exclude underlying diseases like endocrine malfunction. The following should be included in the clinical workup: (1) a thorough personal, obstetric, menstrual, medical, and surgical history; and (2) an assessment of current medications or drug use that may affect fertility. (3) A complete personal male history including: smoking, consanguinity, medical history, surgical history.

Examination:

General examination: Body weight: Being overweight or underweight could have an impact on ovulation (irregular cycle, PCOS). Body temperature: raised owing to progesterone and hair distribution: hirsutism (PCOS).

Abdominal exam: striae (prior pregnancy), mass (ovarian or fibroid), scars, and distribution of hair.

Local inspection: abnormal discharge and pus. Bi-valve speculum: excoriation, erosions, redness, ulcers, and abnormal discharge.

Investigations:

Laboratory workup: Thyroid function to avoid hypothyroidism. Prolactin levels to avoid hypoprolactinemia & random blood glucose to avoid uncontrolled patients with diabetes. Day 3 FSH (≤10 m IU/ ml) and Day 3 LH with estradiol at day 10 of induction. To avoid luteal phase defects and hypoovulation, use progesterone on day 21 or a week before menses begin. Ovarian reserve anti-Mullerian hormone.

In addition to ultrasound evaluation after 1 week of triggering, imaging must involve verification of tubal patency using a hysterosalpingogram or saline infusion sonohysterogram.

Ovulation induction protocols:

From day 2 to day 6, all patients received Clomiphene Citrate (100 mg/day) stimulation to induce enlarged ovarian follicles (diameter >18 mm).

TVS folliculometry performed after 5 days of stimulation in addition to measuring E2 at day 10.

Then triggering achieved by:

After achieving of mature follicle patients are divided into two groups: Group A: 50 patients receive (10.000 IU) Human Chorionic Gonadotrophins (Choriomon) made by IBSA Institute Biochimique SA, CH-6903 Lugano intramuscularly. Group B: 50 patients received (5 IU) Oxytocin (Syntocinon) manufactured by (Sandoz, New jersey, USA) intramuscularly.

Trigger was by HCG (chorimon^©) 10.000 IU / or Oxytocin (Syntocinon) 5IU when lead follicle become =/ >18 mm in all groups.

Signs of ovulation were checked by: The presence or absence of (follicles/corpus luteum) by transvaginal ultrasonography 7 days after Human Chorionic Gonadotropin /or Oxytocin administration.

The patients who achieved Triggering or pregnancy were recorded.

Primary outcome: achieving triggering (checked by TVS folliculometry).

Secondary outcome: achieving pregnancy.

Statistical analysis:

The IBM SPSS software package version 26.0 was used to analyze the data that was supplied to the computer (IBM Corporation, Armonk, NY). Numbers and percentages were used to describe qualitative data. The Kolmogorov-Smirnov test has been employed to ensure that the distribution is normal. The terms "min and max," "mean," "SD," "median," and "interquartile range" (IQR) have been used to describe quantitative data. The obtained findings have been determined to be significant at the 5% level. The chi-square test is used to compare categorical variables between groups. When more than 20% of the cells have an estimated count of less than 5, Monte Carlo correction is used to correct the chi-square. The McNemar and Marginal Homogeneity Tests were used to analyze the significance of the various stages. For normally distributed quantitative variables, the student t-test is used to compare two groups. The paired t-test is used to compare two periods of normally distributed quantitative data. For abnormally distributed quantitative data, the Mann-Whitney test is used to compare two groups. The Wilcoxon signed rank test is used to compare two periods of data with abnormally distributed quantitative parameters. Cochran's test and the Post Hoc Test (Dunn's) are non-parametric tests for binary response variables. Significant was defined as a P value of less than 0.05.

RESULTS

Table 1: Comparison of the two study groups based on their ages (in years)

The mean age in Group A was 24.62 ± 4.10 with range (21-31) and in group B the mean age was 25.66 ± 5.22 with range (21-34). In terms of age, there have been no statistically significant differences between the groups studied (Table 1).

Table 2: Comparison of the two study groups based on the number of follicles, ovulation occurrence, and pregnancy

There was significant difference between studied groups as regard number of follicles. There was no difference between studied groups as regard occurrence of ovulation. In terms of pregnancy, there was no significant difference between the groups studied (Table 2).

Table 3: Comparison of the two study groups based on side effects

In terms of side effects, there have been no significant differences between the groups studied.

Table 4: Comparison of the two study groups based on FSH and LH (Day3)

There was no difference between the study groups based on FSH level. There have been no differences between the study groups based on LH level (Table 4).

Table 5: Comparison of the two study groups based on AMH, E2 level, and BMI

According to AMH, there have been no differences between the studied groups. There have been no differences between the study groups with respect to E2 level. There have been no differences between the studied groups as regards BMI (Table 5).